Isolated from marine dinoflagellate Amphidinium sp., Amphidinolides O and P exhibit cytotoxicity against murine lymphoma L1210 and KB cells. The biological activity and novel 15-membered macrolide structure as well as the difficulties in the isolation of these two Amphidinolides make them interesting targets for total synthesis. The proposed synthesis of Amphidinolides O and P is enantioselective, concise yet flexible and readily applicable to the synthsis of their analogs to study the structure-activity relationships (SAR) of this series of compounds. New synthetic methodogy will be developed in this study with an emphasis on the design of new ligands for chiral catalysis.